Microbial Adaptations to the Psychrosphere/Piezospherejmmb Symposium 93

Total Page:16

File Type:pdf, Size:1020Kb

Microbial Adaptations to the Psychrosphere/Piezospherejmmb Symposium 93 J. Molec. Microbiol. Biotechnol. (1999) 1(1): 93-100. Microbial Adaptations to the Psychrosphere/PiezosphereJMMB Symposium 93 Microbial Adaptations to the Psychrosphere/Piezosphere review genetic and biochemical studies of pressure Douglas H. Bartlett* adaptation by psychrotolerant/psychrophilic piezophilic Center for Marine Biotechnology and Biomedicine prokaryotes with an emphasis on results obtained from Scripps Institution of Oceanography my lab with Photobacterium profundum. Other reviews University of California, San Diego covering high pressure adaptation by low temperature- La Jolla, CA 92093-0202, USA adapted deep-sea organisms include those written by Bartlett (1992), DeLong (1992), Prieur (1992), Somero (1990; 1991; 1992), Bartlett et al., (1995), Yayanos (1995; 1998), Kato and Bartlett (1997), and within this miniseries Abstract symposium the article by Kato and Qureshi. Low temperature and high pressure deep-sea Basis of Pressure Effects environments occupy the largest fraction of the biosphere. Nevertheless, the molecular adaptations The thermodynamic consequences of changes in pressure that enable life to exist under these conditions remain are straightforward. Elevated pressure promotes poorly understood. This article will provide an overview decreased system volume changes associated with the of the current picture on high pressure adaptation in equilibria and rates of biochemical processes. Thus, life in cold oceanic environments, with an emphasis on the deep sea must entail life at low volume change, or genetic experiments performed on Photobacterium other biochemical adjustments which compensate for the profundum. Thus far genes which have been found or consequences of elevated pressure. The relationship of implicated as important for pressure-sensing or pressure to equilibrium and rate processes can be pressure-adaptation include genes required for fatty expressed mathematically as follows: acid unsaturation, the membrane protein genes toxR and rseC and the DNA recombination gene recD. Many 1) Kp = K1 exp(-P∆V/RT) deep-sea bacteria possess genes for the production ‡ of omega-3 polyunsaturated fatty acids. These could and 2) k p = k1 exp(-P∆V /RT) be of biotechnological significance since these fatty acids reduce the risk of cardiovascular disease and These two equations express the relationship of either the certain cancers and are useful as dietary supplements. equilibrium constant (K) or rate constant (k) of a reaction to pressure, as determined by the size of the volume Introduction change that takes place during either the establishment of equilibrium (∆V) or the formation of the activated complex ‡ Low temperature and high pressure environments (the (∆V ). K1 and k1 are the equilibrium and rate constants, psychrosphere and the piezosphere, respectfully) occupy respectively, at atmospheric pressure; Kp and kp are the the largest fractions of the known biosphere in terms of constants at a higher pressure, R is the gas constant and volume. Within these environments psychrophiles exist T is absolute temperature. Because the equilibrium and which can grow at temperatures as low as -12 °C (Russell, rate constants are related to pressure in a logarithmic 1990), and piezophiles (also termed barophiles) exist which fashion, seemingly small changes in volume can lead to can grow at pressures as high as 130 megapascal large changes in K or k. For example, a volume change of [Yayanos, 1998; 1 megapascal (MPa) = 10 bar ≅ 9.9 +50 cm3mol-1 will lead to a 89% inhibition of a rate (or 89% atmospheres]. The lower temperature limit is apparently change in K value) at 100 MPa pressure. A volume change set by the freezing temperature of intracellular water, of +100 cm3mol-1 will lead to a 35% decrease in k or K at whereas the upper pressure limit for life is not known. 10 MPa, and >99% decrease at 100 MPa. Volume changes Although Archaea, particularly those belonging to the accompanying many biological processes (both equilibria nonthermophilic branch within the Crenarchaeota kingdom, and reaction rates) are in the range of approximately 20- are highly abundant in low temperature and high pressure 100 cm3mol-1. Therefore, pressure changes can lead to environments (Fuhrman et al., 1992; DeLong et al., 1994), very substantial alteration (decrease or increase) of all of the cultured psychrotolerant/psychrophilic piezophilic biological activities and structures in the absence of prokaryotes fall within well known lineages of the Bacterial adaptation. domain. Results to date indicate that the adaptations that Because water itself is not highly compressible (about enable these deep-sea microorganisms to grow under low 4% per 100 MPa pressure), the effects of increased temperature and high pressure conditions entail subtle pressure on biochemical processes are not due to effects variations of certain regulatory processes and aspects of stemming from compression of the aqueous medium. cellular architecture present in mesophiles. Here I will briefly However, water structure is very important in pressure sensitivity because changes in hydration of macromolecules and metabolites can lead to substantial *For correspondence. Email [email protected]; Tel. 619-534-5233; Fax. 619-534-7313. alterations in system volume. © 1999 Horizon Scientific Press Further Reading Caister Academic Press is a leading academic publisher of advanced texts in microbiology, molecular biology and medical research. Full details of all our publications at caister.com • MALDI-TOF Mass Spectrometry in Microbiology Edited by: M Kostrzewa, S Schubert (2016) www.caister.com/malditof • Aspergillus and Penicillium in the Post-genomic Era Edited by: RP Vries, IB Gelber, MR Andersen (2016) www.caister.com/aspergillus2 • The Bacteriocins: Current Knowledge and Future Prospects Edited by: RL Dorit, SM Roy, MA Riley (2016) www.caister.com/bacteriocins • Omics in Plant Disease Resistance Edited by: V Bhadauria (2016) www.caister.com/opdr • Acidophiles: Life in Extremely Acidic Environments Edited by: R Quatrini, DB Johnson (2016) www.caister.com/acidophiles • Climate Change and Microbial Ecology: Current Research and Future Trends Edited by: J Marxsen (2016) www.caister.com/climate • Biofilms in Bioremediation: Current Research and Emerging Technologies • Flow Cytometry in Microbiology: Technology and Applications Edited by: G Lear (2016) www.caister.com/biorem Edited by: MG Wilkinson (2015) www.caister.com/flow • Microalgae: Current Research and Applications • Probiotics and Prebiotics: Current Research and Future Trends Edited by: MN Tsaloglou (2016) www.caister.com/microalgae Edited by: K Venema, AP Carmo (2015) www.caister.com/probiotics • Gas Plasma Sterilization in Microbiology: Theory, Applications, Pitfalls and New Perspectives • Epigenetics: Current Research and Emerging Trends Edited by: H Shintani, A Sakudo (2016) Edited by: BP Chadwick (2015) www.caister.com/gasplasma www.caister.com/epigenetics2015 • Virus Evolution: Current Research and Future Directions • Corynebacterium glutamicum: From Systems Biology to Biotechnological Applications Edited by: SC Weaver, M Denison, M Roossinck, et al. (2016) www.caister.com/virusevol Edited by: A Burkovski (2015) www.caister.com/cory2 • Arboviruses: Molecular Biology, Evolution and Control Edited by: N Vasilakis, DJ Gubler (2016) • Advanced Vaccine Research Methods for the Decade of www.caister.com/arbo Vaccines Edited by: F Bagnoli, R Rappuoli (2015) • Shigella: Molecular and Cellular Biology www.caister.com/vaccines Edited by: WD Picking, WL Picking (2016) www.caister.com/shigella • Antifungals: From Genomics to Resistance and the Development of Novel Agents • Aquatic Biofilms: Ecology, Water Quality and Wastewater Edited by: AT Coste, P Vandeputte (2015) Treatment www.caister.com/antifungals Edited by: AM Romaní, H Guasch, MD Balaguer (2016) www.caister.com/aquaticbiofilms • Bacteria-Plant Interactions: Advanced Research and Future Trends Edited by: J Murillo, BA Vinatzer, RW Jackson, et al. (2015) • Alphaviruses: Current Biology www.caister.com/bacteria-plant Edited by: S Mahalingam, L Herrero, B Herring (2016) www.caister.com/alpha • Aeromonas Edited by: J Graf (2015) • Thermophilic Microorganisms www.caister.com/aeromonas Edited by: F Li (2015) www.caister.com/thermophile • Antibiotics: Current Innovations and Future Trends Edited by: S Sánchez, AL Demain (2015) www.caister.com/antibiotics • Leishmania: Current Biology and Control Edited by: S Adak, R Datta (2015) www.caister.com/leish2 • Acanthamoeba: Biology and Pathogenesis (2nd edition) Author: NA Khan (2015) www.caister.com/acanthamoeba2 • Microarrays: Current Technology, Innovations and Applications Edited by: Z He (2014) www.caister.com/microarrays2 • Metagenomics of the Microbial Nitrogen Cycle: Theory, Methods and Applications Edited by: D Marco (2014) www.caister.com/n2 Order from caister.com/order 94 Bartlett Changes in hydrostatic pressure perturb the volume Fatty Acid Regulation of a system without changing its internal energy (as occurs with temperature), or its solvent composition (as occurs Among the evolutionarily adaptive and transiently with pH and osmolarity changes). Thus, pressure is both acclimatory changes thought to be important for growth at a unique and a fundamental thermodynamic parameter. either low temperature or high pressure, membrane fatty acid alterations have received the most attention (Russell Identification of Pressure Sensitive and Hamamoto, 1998; Yayanos, 1998). Both decreased Processes in Mesophilic Microorganisms
Recommended publications
  • DNA Double-Strand Breaks Induced by Reactive Oxygen Species Promote
    bioRxiv preprint doi: https://doi.org/10.1101/533422; this version posted January 29, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 DNA double-strand breaks induced by reactive oxygen 2 species promote DNA polymerase IV activity in 3 Escherichia coli 4 5 Sarah S. Henrikus1,2, Camille Henry3, John P. McDonald4, Yvonne Hellmich5, 6 Elizabeth A. Wood3, Roger Woodgate4, Michael M. Cox3, Antoine M. van Oijen1,2, 7 Harshad Ghodke1,2, Andrew Robinson1,2* 8 1Molecular Horizons Institute and School of Chemistry and Biomolecular Science, University 9 of Wollongong, Wollongong, Australia 10 2Illawarra Health and Medical Research Institute, Wollongong, Australia 11 3Department of Biochemistry, University of Wisconsin-Madison, United States of America 12 4Laboratory of Genomic Integrity, National Institute of Child Health and Human 13 Development, National Institutes of Health, Bethesda, Maryland, United States of America 14 5Institute of Biochemistry, Goethe Universität, Frankfurt, Germany 15 *Corresponding author. Mailing address: School of Chemistry, University of Wollongong, 16 Wollongong, NSW 2500, Australia. Email: [email protected]. 17 1 bioRxiv preprint doi: https://doi.org/10.1101/533422; this version posted January 29, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 Under many conditions the killing of bacterial cells by antibiotics is potentiated by 2 DNA damage induced by reactive oxygen species (ROS)1–3. A primary cause of ROS- 3 induced cell death is the accumulation of DNA double-strand breaks (DSBs)1,4–6.
    [Show full text]
  • Vibrio Cholerae Filamentation Promotes Chitin Surface Attachment at the Expense of Competition in Biofilms
    Vibrio cholerae filamentation promotes chitin surface attachment at the expense of competition in biofilms Benjamin R. Wuchera, Thomas M. Bartlettb, Mona Hoyosc, Kai Papenfortc, Alexandre Persatd,e, and Carey D. Nadella,1 aDepartment of Biological Sciences, Dartmouth College, Hanover, NH 03755; bDepartment of Microbiology, Harvard Medical School, Boston, MA 02115; cDepartment of Microbiology, Faculty of Biology I, Ludwig Maximilians University of Munich, 82152 Martinsried, Germany; dInstitute of Bioengineering, School of Life Sciences, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland; and eGlobal Health Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland Edited by Thomas J. Silhavy, Princeton University, Princeton, NJ, and approved June 3, 2019 (received for review November 13, 2018) Collective behavior in spatially structured groups, or biofilms, is the adapted to colonize chitin surfaces, exploit the resources em- norm among microbes in their natural environments. Though bedded in them, and spread to other particles are thus likely to biofilm formation has been studied for decades, tracing the be more frequently represented in estuarine conditions (20, 21). mechanistic and ecological links between individual cell morphol- The marine natural history of V. cholerae makes this bacterium ogies and the emergent features of cell groups is still in its infancy. an ideal candidate for studying the effects of different surface- Here we use single-cell–resolution confocal microscopy to explore occupation strategies that might occur in estuarine and oceanic biofilms of the human pathogen Vibrio cholerae in conditions environments (16, 18, 20, 22, 23). mimicking its marine habitat. Prior reports have noted the occurrence Many strains of V.
    [Show full text]
  • Downloaded from Bindingdb ( Et Al., 2006) Used As a Reference Database
    Development of evolution drugs - antibacterial compounds that block pathways to resistance. Yanmin Zhang1,2#, Sourav Chowdhury2#, João V. Rodrigues 2, Eugene. Shakhnovich2 1School of Science, China Pharmaceutical University 639 Longmian Avenue, Jiangning District Nanjing, Jiangsu 211198 P.R China 2Department of Chemistry and Chemical Biology Harvard University 12 Oxford Street Cambridge MA 02138 # contributed equally Abstract Antibiotic resistance is a worldwide challenge. A potential approach to block resistance is to simultaneously inhibit WT and known escape variants of the target bacterial protein. Here we applied an integrated computational and experimental approach to discover compounds that inhibit both WT and trimethoprim (TMP) resistant mutants of E. coli dihydrofolate reductase (DHFR). We identified a novel compound (CD15-3) that inhibits WT DHFR and its TMP resistant variants L28R, P21L and A26T with IC50 50-75 µM against WT and TMP-resistant strains. Resistance to CD15-3 was dramatically delayed compared to TMP in in vitro evolution. Whole genome sequencing of CD15-3 resistant strains showed no mutations in the target folA locus. Rather, gene duplication of several efflux pumps gave rise to weak (about twofold increase in IC50) resistance against CD15-3. Altogether, our results demonstrate the promise of strategy to develop evolution drugs - compounds which block evolutionary escape routes in pathogens. 1. Introduction Fast paced artificial selection in bacteria against common antibiotics has led to the emergence of highly resistant bacterial strains which potentially render a wide variety of antibiotics clinically ineffective. Emergence of these “superbugs” including ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) (Peneş et al., 2017) call for novel approaches to design antibiotic compounds that act as “evolution drugs” by blocking evolutionary escape from antibiotic stressor.
    [Show full text]
  • Filamentation by Escherichia Coli Subverts Innate Defenses During Urinary Tract Infection
    Filamentation by Escherichia coli subverts innate defenses during urinary tract infection Sheryl S. Justice*†, David A. Hunstad*‡, Patrick C. Seed*‡§, and Scott J. Hultgren* Departments of *Molecular Microbiology and ‡Pediatrics, Washington University School of Medicine, St. Louis, MO 63110 Edited by M. J. Osborn, University of Connecticut Health Center, Farmington, CT, and approved November 8, 2006 (received for review July 26, 2006) To establish disease, an infecting organism must overcome a vast initial UTI. Many women use antibiotics daily to reduce the risk array of host defenses. During cystitis, uropathogenic Escherichia of recurrence only to suffer recrudescence when this prophylac- coli (UPEC) subvert innate defenses by invading superficial um- tic regimen is discontinued. The use of in vitro and in vivo models brella cells and rapidly increasing in numbers to form intracellular has allowed the description of events that delineate the acute and bacterial communities (IBCs). In the late stages of the IBC pathway, chronic stages of UTI. Mannosylated uroplakin proteins coating filamentous and bacillary UPEC detach from the biofilm-like IBC, the surface of the superficial umbrella cells of the bladder serve fluxing out of this safe haven to colonize the surrounding epithe- as the receptors for binding and invasion of UPEC by means of lium and initiate subsequent generations of IBCs, and eventually the FimH adhesin at the tips of type 1 pili (3, 4). During murine they establish a quiescent intracellular reservoir. Filamentous UPEC cystitis, intracellular bacterial communities (IBCs) appear ini- are not observed during acute infection in mice lacking functional tially as rod-shaped, loosely organized colonies with a doubling Toll-like receptor 4 (TLR4), suggesting that the filamentous phe- time of 30 min (5).
    [Show full text]
  • Activation of the Saccharomyces Cerevisiae Filamentation/Invasion Pathway by Osmotic Stress in High-Osmolarity Glycogen Pathway Mutants
    Copyright 1999 by the Genetics Society of America Activation of the Saccharomyces cerevisiae Filamentation/Invasion Pathway by Osmotic Stress in High-Osmolarity Glycogen Pathway Mutants K. D. Davenport, K. E. Williams, B. D. Ullmann and M. C. Gustin Department of Biochemistry and Cell Biology, Rice University, Houston, Texas 77005-1892 Manuscript received January 7, 1999 Accepted for publication July 6, 1999 ABSTRACT Mitogen-activated protein kinase (MAPK) cascades are frequently used signal transduction mechanisms in eukaryotes. Of the ®ve MAPK cascades in Saccharomyces cerevisiae, the high-osmolarity glycerol response (HOG) pathway functions to sense and respond to hypertonic stress. We utilized a partial loss-of-function mutant in the HOG pathway, pbs2-3, in a high-copy suppressor screen to identify proteins that modulate growth on high-osmolarity media. Three high-copy suppressors of pbs2-3 osmosensitivity were identi®ed: MSG5, CAK1, and TRX1. Msg5p is a dual-speci®city phosphatase that was previously demonstrated to dephosphorylate MAPKs in yeast. Deletions of the putative MAPK targets of Msg5p revealed that kss1D could suppress the osmosensitivity of pbs2-3. Kss1p is phosphorylated in response to hyperosmotic shock in a pbs2-3 strain, but not in a wild-type strain nor in a pbs2-3 strain overexpressing MSG5. Both TEC1 and FRE::lacZ expressions are activated in strains lacking a functional HOG pathway during osmotic stress in a ®lamentation/invasion-pathway-dependent manner. Additionally, the cellular projections formed by a pbs2-3 mutant on high osmolarity are absent in strains lacking KSS1 or STE7. These data suggest that the loss of ®lamentation/invasion pathway repression contributes to the HOG mutant phenotype.
    [Show full text]
  • Developing Rapid Antimicrobial Susceptibility Testing for Motile/Non
    biosensors Article Developing Rapid Antimicrobial Susceptibility Testing for Motile/Non-Motile Bacteria Treated with Antibiotics Covering Five Bactericidal Mechanisms on the Basis of Bead-Based Optical Diffusometry Yao-Tzu Yang 1, Jhih-Cheng Wang 2 and Han-Sheng Chuang 1,3,* 1 Department of Biomedical Engineering, National Cheng Kung University, Tainan 70101, Taiwan; [email protected] 2 Department of Urology, Chi-Mei Medical Center, Tainan 71004, Taiwan; [email protected] 3 Center for Micro/Nano Science and Technology, National Cheng Kung University, Tainan 70101, Taiwan * Correspondence: [email protected] Received: 17 September 2020; Accepted: 17 November 2020; Published: 19 November 2020 Abstract: Rapid antimicrobial susceptibility testing (AST) is an effective measure in the treatment of infections and the prevention of bacterial drug resistance. However, diverse antibiotic types and bacterial characteristics have formed complicated barriers to rapid diagnosis. To counteract these limitations, we investigated the interactions between antibiotic-treated bacteria and functionalized microbeads in optical diffusometry. The conjugation with bacteria increased the effective microbead complex size, thereby resulting in a temporal diffusivity change. The yielded data were sorted and analyzed to delineate a pattern for the prediction of antimicrobial susceptibility. The outcome showed that a completed rapid AST based on the trend of microbead diffusivity could provide results within 3 h (2 h measurement + 1 h computation). In this research, we studied four bacterial strains, including Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Staphylococcus aureus, and six antibiotics. Despite the different inhibitory effects caused by various antibiotics, similar trends in diffusivity alteration for all susceptible and resistant cases in the last 40 min of the 2-h measurement period were deduced.
    [Show full text]
  • Bacterial Filament Division Dynamics Allows Rapid Post-Stress Cell
    bioRxiv preprint doi: https://doi.org/10.1101/2020.03.16.993345; this version posted March 16, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. 1 Bacterial filament division dynamics allows rapid post-stress cell proliferation 2 3 4 Julien Cayron1, Annick Dedieu1, Christian Lesterlin1* 5 6 7 Affiliations: 8 1Microbiologie Moléculaire et Biochimie Structurale (MMSB), Université Lyon 1, 9 CNRS, Inserm, UMR5086, 69007, Lyon, France 10 *Correspondence to: [email protected] 11 12 13 Keywords: 14 Bacterial filaments, exit from filamentation, cell division, chromosome intracellular 15 organisation, stress response, real-time microscopy in live-cells. 16 17 18 One Sentence Summary: 19 Bacterial filaments recover by successive, frequent and Min-dependent asymmetric 20 tip-divisions that rapidly produce multiple daughter cells with normal size and 21 viability 22 bioRxiv preprint doi: https://doi.org/10.1101/2020.03.16.993345; this version posted March 16, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. 23 Abstract 24 Many bacterial species grow into filaments under stress conditions. Initially regarded 25 as an indicator of cell death, filamentation is now proposed to be a transient 26 morphological change that improves bacterial survival in hostile environments.
    [Show full text]
  • The Role of Cytoskeletal Elements in Shaping Bacterial Cells Hongbaek Cho*
    J. Microbiol. Biotechnol. (2015), 25(3), 307–316 http://dx.doi.org/10.4014/jmb.1409.09047 Research Article Review jmb The Role of Cytoskeletal Elements in Shaping Bacterial Cells Hongbaek Cho* Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA Received: September 16, 2014 Revised: September 26, 2014 Beginning from the recognition of FtsZ as a bacterial tubulin homolog in the early 1990s, many Accepted: September 26, 2014 bacterial cytoskeletal elements have been identified, including homologs to the major eukaryotic cytoskeletal elements (tubulin, actin, and intermediate filament) and the elements unique in prokaryotes (ParA/MinD family and bactofilins). The discovery and functional First published online characterization of the bacterial cytoskeleton have revolutionized our understanding of September 29, 2014 bacterial cells, revealing their elaborate and dynamic subcellular organization. As in *Corresponding author eukaryotic systems, the bacterial cytoskeleton participates in cell division, cell morphogenesis, Phone: +1-617-432-6970; DNA segregation, and other important cellular processes. However, in accordance with the Fax: +1-617-432-6970; vast difference between bacterial and eukaryotic cells, many bacterial cytoskeletal proteins E-mail: hongbaek_cho@hms. harvard.edu play distinct roles from their eukaryotic counterparts; for example, control of cell wall synthesis for cell division and morphogenesis. This review is aimed at providing an overview of the bacterial cytoskeleton, and discussing the roles and assembly dynamics of bacterial cytoskeletal proteins in more detail in relation to their most widely conserved functions, DNA pISSN 1017-7825, eISSN 1738-8872 segregation and coordination of cell wall synthesis. Copyright© 2015 by The Korean Society for Microbiology Keywords: Bacterial cytoskeleton, DNA segregation, FtsZ, MreB, ParA, peptidoglycan and Biotechnology Introduction cytokinesis, and cell morphogenesis.
    [Show full text]
  • Antibiotic Acyldepsipeptides Activate Clpp Peptidase to Degrade the Cell Division Protein Ftsz
    Antibiotic acyldepsipeptides activate ClpP peptidase to degrade the cell division protein FtsZ Peter Sassa,b, Michaele Jostena, Kirsten Famullab, Guido Schifferc, Hans-Georg Sahla, Leendert Hamoend, and Heike Brötz-Oesterheltb,1 aInstitute of Medical Microbiology, Immunology, and Parasitology, Pharmaceutical Microbiology Unit, University of Bonn, 53115 Bonn, Germany; bInstitute for Pharmaceutical Biology, University of Düsseldorf, 40204 Düsseldorf, Germany; cAiCuris GmbH & Co. KG, 42117 Wuppertal, Germany; and dCentre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle NE2 4AX, United Kingdom Edited* by Richard P. Novick, New York University School of Medicine, New York, New York, and approved September 11, 2011 (received for review June 27, 2011) The worldwide spread of antibiotic-resistant bacteria has lent ur- bacterial ATP-dependent caseinolytic protease. The Clp pro- gency to the search for antibiotics with new modes of action that tease is a crucial factor in maintaining vital cellular functions in are devoid of preexisting cross-resistances. We previously de- protein quality control and protein homeostasis as well as in scribed a unique class of acyldepsipeptides (ADEPs) that exerts controlling developmental processes like cell motility, genetic prominent antibacterial activity against Gram-positive pathogens competence, cell differentiation, and sporulation (13, 14). ClpP including streptococci, enterococci, as well as multidrug-resistant is a tightly regulated protein, which is unable to degrade proteins Staphylococcus aureus. Here, we report that ADEP prevents cell on its own, and strictly depends on Clp ATPases and accessory division in Gram-positive bacteria and induces strong filamenta- proteins for proteolytic activation (15). The Gram-positive model tion of rod-shaped Bacillus subtilis and swelling of coccoid S.
    [Show full text]
  • Emergence of Antibiotic Resistance from Multinucleated Bacterial Filaments
    Emergence of antibiotic resistance from multinucleated bacterial filaments Julia Bosa, Qiucen Zhangb, Saurabh Vyawaharea, Elizabeth Rogersc, Susan M. Rosenbergc, and Robert H. Austina,1 aDepartment of Physics, Princeton University, Princeton, NJ 08544-0708; bDepartment of Physics, University of Illinois at Urbana–Champaign, Urbana, IL 61801- 3080; and cDepartments of Molecular and Human Genetics, Biochemistry and Molecular Biology, and Molecular Virology and Microbiology, and the Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030 Contributed by Robert H. Austin, November 3, 2014 (sent for review August 26, 2014) Bacteria can rapidly evolve resistance to antibiotics via the SOS sized offspring cells (8). However, the mechanisms underlying the response, a state of high-activity DNA repair and mutagenesis. We evolution of filamentous bacteria when the selective pressure is explore here the first steps of this evolution in the bacterium maintained have been poorly described, in part because most studies Escherichia coli. Induction of the SOS response by the genotoxic have used stress conditions that were evolutionarily unfavorable and antibiotic ciprofloxacin changes the E. coli rod shape into multichro- instead led to irreversible bacterial growth arrest and/or rapid death. mosome-containing filaments. We show that at subminimal inhib- Bacterial cell-division arrest resulting from inhibition of DNA itory concentrations of ciprofloxacin the bacterial filament divides replication after cipro exposure (2) is caused by the induction of asymmetrically repeatedly at the tip. Chromosome-containing buds a division inhibitor (e.g., SulA in E. coli) (13, 15). sulA gene in- are made that, if resistant, propagate nonfilamenting progeny with duction is part of a set of over 30 induced genes involved in DNA enhanced resistance to ciprofloxacin as the parent filament dies.
    [Show full text]
  • Gram-Negative Synergy and Mechanism of Action of Alkynyl
    www.nature.com/scientificreports OPEN Gram-negative synergy and mechanism of action of alkynyl bisbenzimidazoles Received: 10 August 2018 Jordan Chamberlin1, Sandra Story2, Nihar Ranjan1,3, Geofrey Chesser1 & Dev P. Arya 1,2 Accepted: 15 August 2019 Bisbenzimidazoles with terminal alkynyl linkers, selective inhibitors of bacterial topoisomerase I, have Published: xx xx xxxx been evaluated using bacterial cytological profling (BCP) to ascertain their mechanism of action and screened for synergism to improve Gram-negative bacterial coverage. Principal component analysis of high throughput fuorescence images suggests a dual-mechanism of action afecting DNA synthesis and cell membrane integrity. Fluorescence microscopy of bacteria challenged with two of the alkynyl- benzimidazoles revealed changes in the cellular ultrastructure that difered from topoisomerase II inhibitors including induction of spheroplasts and membrane lysis. The cytoskeleton recruitment enzyme inhibitor A22 in combination with one of the alkynyl-benzimidazoles was synergistic against Acinetobacter baumannii and Escherichia coli. Gram-positive coverage remained unchanged in the A22-alkynyl bisbenzimidazole combination. Efux inhibitors were not synergistic, suggesting that the Gram-negative outer membrane was a signifcant barrier for alkynyl-bisbenzimidazole uptake. Time- kill assays demonstrated the A22-bisbenzimidazole combination had a similar growth inhibition curve to that of norfoxacin in E.coli. Bisbenzimidazoles with terminal alkynyl linkers likely impede bacterial growth by compromising cell membrane integrity and by interfering with DNA synthesis against Gram- positive pathogens and in the synergistic combination against Gram-negative pathogens including E. coli and multidrug-resistant A. baumanii. Tere is a dire need for new classes of antibiotics with novel mechanisms of action (MOA), for which there are currently few options.
    [Show full text]
  • Global Analysis of Fungal Morphology Exposes Mechanisms of Host Cell Escape
    ARTICLE Received 4 Nov 2014 | Accepted 24 Feb 2015 | Published 31 Mar 2015 DOI: 10.1038/ncomms7741 OPEN Global analysis of fungal morphology exposes mechanisms of host cell escape Teresa R. O’Meara1,*, Amanda O. Veri1,*, Troy Ketela1, Bo Jiang2, Terry Roemer3 & Leah E. Cowen1 Developmental transitions between single-cell yeast and multicellular filaments underpin virulence of diverse fungal pathogens. For the leading human fungal pathogen Candida albicans, filamentation is thought to be required for immune cell escape via induction of an inflammatory programmed cell death. Here we perform a genome-scale analysis of C. albicans morphogenesis and identify 102 negative morphogenetic regulators and 872 positive regulators, highlighting key roles for ergosterol biosynthesis and N-linked glycosylation. We demonstrate that C. albicans filamentation is not required for escape from host immune cells; instead, macrophage pyroptosis is driven by fungal cell-wall remodelling and exposure of glycosylated proteins in response to the macrophage phagosome. The capacity of killed, previously phagocytized cells to drive macrophage lysis is also observed with the distantly related fungal pathogen Cryptococcus neoformans. This study provides a global view of morphogenetic circuitry governing a key virulence trait, and illuminates a new mechanism by which fungi trigger host cell death. 1 Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada M5S 1A8. 2 Bioprocess Technology & Expression, Merck Research Laboratories, 2000 Galloping Hill Rd, Kenilworth, New Jersey 07033, USA. 3 Department of Infectious Diseases, Merck Research Laboratories, 2000 Galloping Hill Rd, Kenilworth, New Jersey 07033, USA. * These authors contributed equally to this work. Correspondence and requests for materials should be addressed to L.E.C.
    [Show full text]